The proposed research program will focus on certain intrinsic functions of vascular endothelium and smooth muscle which contribute to normal cardiovascular homeostasis. Using available, as well as newly developed techniques, pure populations of each cell type will be isolated and cultured from human and experimental animal blood vessels. The following features will be studied: endogenous prostaglandin production, and the effect of vasoactive substances and inflammatory mediators on this process; the presence of angiotensin I converting enzyme and variations in its activity under different experimental conditions; the presence of specific receptors for angiotensin II and prostaglandins, and factors controlling their regulation. Extension of the above studies to blood vessel cells isolated from spontaneously hypertensive rats may help define pathogenetic mechanisms in altered vascular homeostasis.